The Role of APO‐1‐Mediated Apoptosis in the Immune System

Abstract

B and T lymphocytes contact antigen at different stages of maturation and in a different cellular context. Depending on these circumstances, their responses can be entirely different. Immature double-positive (CD4"^/CD8^) thymocytes can be positively selected and exit the thymus to populate the peripheral immune system. Alternatively, autoreactive thymocytes are negatively selected and die within the thymus by programmed cell death, apoptosis. A similar process, albeit less well defined, might be operative for immature B cells in bone marrow. These events are the basis of self-tolerance and generate lymphocytes that react with foreign antigens. Under the appropriate conditions, antigen stimulation of resting mature lymphocytes in the peripheral lymphoid organs can induce expansion of the reactive lymphocyte pool or anergy in the absence of costimulatory signals. In previously activated lymphocytes, triggering of the antigen receptor may lead to proliferation and memory or to death by apoptosis. The molecular switches leading to these different responses are partially unknown. Apoptosis in the peripheral lymphoid system may serve several functions. It may be a second safeguard to assure self-tolerance and control autoreactive cells that arise in the periphery from cells that have escaped tolerization in the central lymphoid organs. In addition, apoptosis may prevent uncontrolled expansion of specific, antigen-reactive lymphocytes and may be one mechanism of immunosuppression (Krammer et